Abstract 14870: Clinical Impact of Cardiovascular Diseases in Rasopathies
Background: — RASopathies constitute a family of disorders with a specific cardiac phenotype, but a detailed characterization of cardiac morbidity and mortality is lacking. Aim of this study was to analyze these data, collected by different cardiac centers.
Methods and Results: — A multi-centric, observational, retrospective cohort study was conducted in seven cardiac centers, participating to the CArdiac Rasopathy NETwork (CARNET). 371 patients with confirmed molecular diagnosis of RASopathy were reviewed. Mortality was described as crude mortality, cumulative survival and restricted estimated mean survival. Multivariable regression analysis was used to study the effect of each mutated gene on cardiac defects, number of interventions and prognosis.
Cardiac defects were found in 80.3% of cases. More than half had pulmonary stenosis (PS), followed by hypertrophic cardiomyopathy (HCM)and atrioventricular canal defect (AVC). RAF1 mutations were the best predictors of cardiac involvement. RAF1 and BRAF mutations were positively associated with HCM, while PTPN11 defects with AVC and PS. Among patients with heart disease (n=298), almost half underwent intervention. A second procedure was required in 41%, mainly for recurrent PS. Mortality was relatively low. Patients with HCM and age < 2 years or young adults, with biventricular obstruction and PTPN11 mutations, had higher risk of cardiac death. Overall, crude mortality was 0.29/100 patients-year. Cumulative survival was 98.8%, 98.2%, 97.7%, 90.2%, at 1, 5, 10, and 25 years, respectively. Restricted estimated mean survival at 25 years follow-up was 24.2 years.
Conclusions: — In this large cohort of RASopathy patients, cardiac involvement was common and required at least one intervention in almost half of cases. The risk of intervention was higher in individuals with Noonan syndrome and PS carrying PTPN11 mutations, and lower among patients with Costello syndrome and cardiofaciocutaneous syndrome. Mortality was relatively low, however, the association between HCM, aPTPN11 mutations and biventricular outflow tract obstructions, may predict early mortality.
Author Disclosures: G. Calcagni: None. G. Limongelli: None. A. d’Ambrosio: None. F. Gesualdo: None. M. Digilio: None. A. Baban: None. S. Albanese: None. P. Versacci: None. E. de Luca: None. G. Ferrero: None. G. Baldassarre: None. G. Agnoletti: None. E. Banaudi: None. J. Marek: None. J. Kaski: None. G. Tuo: None. M. Russo: None. G. Pacileo: None. O. Milanesi: None. D. Messina: None. M. Marasini: None. F. Cairello: None. R. Formigari: None. M. Brighenti: None. B. Dallapiccola: None. M. Tartaglia: None. B. Marino: None.
- © 2016 by American Heart Association, Inc.